Process for production of optically active 2-substituted propanal derivative

Abstract

The present invention relates to a process for producing an optically active 2-substituted propanal derivative, and more particularly, a process for producing an optically active 2-substituted propanal derivative which comprises stereoselectively reducing a carbon-carbon double bond of a 2-substituted acrolein derivative by using an enzyme source capable of stereoselectively reducing said carbon-carbon double bond. According to the present invention, it becomes possible to produce an optically active 2-substituted propanal derivative, in particular an optically active 2-alkylpropanal derivative, which is useful as an intermediate of pharmaceutical products, sweetening agents, etc., in a convenient manner from inexpensive and easily available materials.

1 . A process for producing an optically active 2-substituted propanal derivative represented by the general formula (2): 
       
         
           
           
               
               
           
         
       
       (in the formula, R is a methyl group having a substituent, an alkyl group containing 2 to 10 carbon atoms which may optionally be substituted, or an aralkyl group containing 5 to 15 carbon atoms which may optionally be substituted, and * is an asymmetric carbon)
 which comprises reacting a 2-substituted acrolein derivative represented by the general formula (1): 
 
       
         
           
           
               
               
           
         
       
       (in the formula, R is as mentioned above) with an enzyme source capable of stereoselectively reducing the carbon-carbon double bond of the 2-substituted acrolein derivative. 
     
     
         2 . The process according to  claim 1 ,
 wherein R is an alkyl group containing 2 to 10 carbon atoms which may optionally be substituted.   
     
     
         3 . The process according to  claim 1 ,
 wherein R is an alkyl group containing 2 to 4 carbon atoms which may optionally be substituted.   
     
     
         4 . The process according to  claim 1 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Candida , the genus  Kluyveromyces , the genus  Pichia , the genus  Rhodotorula , the genus  Saccharomyces , the genus  Sporidiobolus , the genus  Spolobolomyces , the genus  Trigonopsis , the genus  Zygosaccharomyces , the genus  Achromobacter , the genus  Acidiphilium , the genus  Alcaligenes , the genus  Arthrobacter , the genus  Bacillus , the genus  Corynebacterium , the genus  Escherichia , the genus  Micrococcus , the genus  Pseudomonas , the genus  Paenibacillus , or the genus  Xanthomonas.      
     
     
         5 . The process according to  claim 1 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Candida , the genus  Kluyveromyces , the genus  Pichia , the genus  Rhodotorula , the genus  Saccharomyces , the genus  Sporidiobolus , the genus  Spolobolomyces , the genus  Trigonopsis , the genus  Zygosaccharomyces , the genus  Acidiphilium , the genus  Arthrobacter , the genus  Bacillus , the genus  Micrococcus , the genus  Pseudomonas , the genus  Paenibacillus , or the genus  Xanthomonas , and capable of R-selective reduction of the carbon-carbon double bond of the compound represented by the above formula (1).   
     
     
         6 . The process according to  claim 5 ,
 wherein said enzyme source capable of R-selective reduction is an enzyme source derived from one or more microorganism(s) selected from the group consisting of  Candida cantarellii, Candida etchellsii, Candida kefyr, Candida musae, Candida nitratophila, Candida sake, Candida stellata, Candida zeylanoides, Kluyveromyces lactis  var.  drosphilarum, Pichia membranaefaciens, Pichia heedii, Rhodotorula minuta, Saccharomyces unisporus, Saccharomyces bayanus, Saccharomyces cerevisiae, Saccharomyces castellii, Saccharomyces pastorianus, Sporidiobolus johnsonii, Sporidiobolus salmonicolor, Spolobolomyces salmonicolor, Trigonopsis variabilis, Zygosaccharomyces bailii, Arthrobacter nicotianae, Acidiphilium cryptum, Bacillus cereus, Bacillus coagulans, Bacillus licheniformis, Bacillus pumilus, Bacillus badius, Bacillus sphaericus, Micrococcus luteus, Pseudomonas stutzeri, Pseudomonas fragi, Pseudomonas putida, Paenibacillus alvei , and  Xanthomonas  sp.   
     
     
         7 . The process according to  claim 5 ,
 wherein said enzyme source capable of R-selective reduction is a cultured product of a transformed microorganism transformed with a vector containing a gene of NADPH dehydrogenase derived from  Saccharomyces cerevisiae  (Old Yellow Enzyme 2).   
     
     
         8 . The process according to  claim 1 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Achromobacter , the genus  Alcaligenes , the genus  Arthrobacter , the genus  Corynebacterium , or the genus  Escherichia , and capable of S-selective reduction of the carbon-carbon double bond of the compound represented by the above formula (1).   
     
     
         9 . The process according to  claim 8 ,
 wherein said enzyme source capable of S-selective reduction is an enzyme source derived from one or more microorganism(s) selected from the group consisting of  Achromobacter xylosoxidans  subsp.  denitrificans, Alcaligenes faecalis, Alcaligenes  sp.,  Arthrobacter crystallopoietes, Arthrobacter protophormise, Corynebacterium ammoniagenes , and  Escherichia coli.      
     
     
         10 . The process according to  claim 1 ,
 wherein an oxidoreductase classified into Enzyme Commission Number 1.6.99 is used as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond.   
     
     
         11 . The process according to  claim 10 ,
 wherein NADPH dehydrogenase classified into EC 1.6.99.1 is used as the oxidoreductase classified into Enzyme Commission Number 1.6.99, and   an R form of the compound represented by the above formula (2) is produced.   
     
     
         12 . The process according to  claim 11 ,
 wherein said NADPH dehydrogenase is NADPH dehydrogenase derived from  Saccharomyces cerevisiae  (Old Yellow Enzyme 2).   
     
     
         13 . The process according to  claim 2 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Candida , the genus  Kluyveromyces , the genus  Pichia , the genus  Rhodotorula , the genus  Saccharomyces , the genus  Sporidiobolus , the genus  Spolobolomyces , the genus  Trigonopsis , the genus  Zygosaccharomyces , the genus  Achromobacter , the genus  Acidiphilium , the genus  Alcaligenes , the genus  Arthrobacter , the genus  Bacillus , the genus  Corynebacterium , the genus  Escherichia , the genus  Micrococcus , the genus  Pseudomonas , the genus  Paenibacillus , or the genus  Xanthomonas.      
     
     
         14 . The process according to  claim 3 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Candida , the genus  Kluyveromyces , the genus  Pichia , the genus  Rhodotorula , the genus  Saccharomyces , the genus  Sporidiobolus , the genus  Spolobolomyces , the genus  Trigonopsis , the genus  Zygosaccharomyces , the genus  Achromobacter , the genus  Acidiphilium , the genus  Alcaligenes , the genus  Arthrobacter , the genus  Bacillus , the genus  Corynebacterium , the genus  Escherichia , the genus  Micrococcus , the genus  Pseudomonas , the genus  Paenibacillus , or the genus  Xanthomonas.      
     
     
         15 . The process according to  claim 2 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Candida , the genus  Kluyveromyces , the genus  Pichia , the genus  Rhodotorula , the genus  Saccharomyces , the genus  Sporidiobolus , the genus  Spolobolomyces , the genus  Trigonopsis , the genus  Zygosaccharomyces , the genus  Acidiphilium , the genus  Arthrobacter , the genus  Bacillus , the genus  Micrococcus , the genus  Pseudomonas , the genus  Paenibacillus , or the genus  Xanthomonas , and capable of R-selective reduction of the carbon-carbon double bond of the compound represented by the above formula (1).   
     
     
         16 . The process according to  claim 3 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Candida , the genus  Kluyveromyces , the genus  Pichia , the genus  Rhodotorula , the genus  Saccharomyces , the genus  Sporidiobolus , the genus  Spolobolomyces , the genus  Trigonopsis , the genus  Zygosaccharomyces , the genus  Acidiphilium , the genus  Arthrobacter , the genus  Bacillus , the genus  Micrococcus , the genus  Pseudomonas , the genus  Paenibacillus , or the genus  Xanthomonas , and capable of R-selective reduction of the carbon-carbon double bond of the compound represented by the above formula (1).   
     
     
         17 . The process according to  claim 2 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Achromobacter , the genus  Alcaligenes , the genus  Arthrobacter , the genus  Corynebacterium , or the genus  Escherichia , and capable of S-selective reduction of the carbon-carbon double bond of the compound represented by the above formula (1).   
     
     
         18 . The process according to  claim 3 ,
 which comprises using, as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond, an enzyme source derived from a microorganism belonging to the genus  Achromobacter , the genus  Alcaligenes , the genus  Arthrobacter , the genus  Corynebacterium , or the genus  Escherichia , and capable of S-selective reduction of the carbon-carbon double bond of the compound represented by the above formula (1).   
     
     
         19 . The process according to  claim 2 ,
 wherein an oxidoreductase classified into Enzyme Commission Number 1.6.99 is used as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond.   
     
     
         20 . The process according to  claim 3 ,
 wherein an oxidoreductase classified into Enzyme Commission Number 1.6.99 is used as the enzyme source capable of stereoselectively reducing the carbon-carbon double bond.